A gain-of-function mouse model identifies PRMT6 as a NF-κB coactivator

Area of Science:

• Molecular Biology
• Epigenetics
• Gene Regulation

Background:

• Protein arginine methyltransferase 6 (PRMT6) is a nuclear enzyme involved in histone modification.
• Understanding PRMT6's in vivo function requires specific experimental models.

Purpose of the Study:

• To elucidate the biological function of PRMT6 in vivo.
• To investigate the mechanism by which PRMT6 influences gene expression.

Main Methods:

• Generation of transgenic mice expressing a tamoxifen-inducible ER*-PRMT6 fusion protein.
• Analysis of histone modifications (H3R2me2a) and cytokine (IL-6) levels upon PRMT6 activation.
• Investigation of PRMT6 interaction with the NF-κB pathway, including RelA binding and promoter recruitment.

Main Results:

• Tamoxifen treatment stabilized ER*-PRMT6, leading to nuclear translocation and increased H3R2me2a marks.
• Induced PRMT6 activation resulted in elevated IL-6 levels, mediated by the NF-κB pathway.
• PRMT6 directly interacts with RelA, acts as a coactivator, and is recruited to NF-κB target promoters.

Conclusions:

• PRMT6 functions as a coactivator of the NF-κB pathway.
• PRMT6 is recruited to specific NF-κB target gene promoters, influencing transcription through histone modifications or other chromatin-associated protein methylation.